姜黄素调控DC细胞mGluR4/cAMP/PTEN信号轴影响Th17分化治疗白癜风的机制研究

中医“从血论治”理论指导白癜风的临床施治具有较好疗效，代表中药姜黄可促进黑素合成治疗白癜风，但其具体机制尚未明晰。申请人前期研究明确了姜黄作为君药的中药组方可影响黑素合成，进一步实验发现其主要活性成分姜黄素可激活代谢型谷氨酸受体4（mGluR4）通路，抑制Th17细胞相关因子的产生。Th17细胞异常活化正是影响白癜风发病的重要因素。本项目拟在此工作基础上，提取原代培养的小鼠骨髓源性树突状细胞，敲减mGluR4，同时分别加入cAMP、PTEN抑制剂，与CD4+T细胞共培养，以共培养上清处理B16黑素瘤细胞，揭示姜黄素通过mGluR4/cAMP/PTEN信号轴抑制Th17分化促进黑素合成的分子机制。最后，基于白癜风小鼠模型的建立，明确姜黄素促进黑素合成的作用机制。本研究在动物、细胞、分子三个层次开展系统研究，有助于揭示白癜风的神经-免疫发病机制，为白癜风的中西医结合治疗提供新策略。

Vitiligo can be well treated by doctors under the guidance of the traditional Chinese medicine theory of "Treating By Regulating Blood". The representative Chinese medicine turmeric can promote melanogenesis to treat vitiligo. However, the specific mechanism has not yet been clarified. Our previous research found that Chinese herbal formulas, of which turmeric as the sovereign drug, affected melanogenesis. And furthermore curcumin, the main active ingredient of turmeric, inhibited the production of Th17-related factors by activating the metabotropic glutamate receptor 4 (mGluR4) pathway. Abnormal activation of Th17 cells plays an important role in the pathogenesis of vitiligo. In this study we intend to primarily culture mouse bone marrow derived dendritic cells (BMDC), knock down mGluR4, and simultaneously add the inhibitors of cAMP and PTEN, co-culture the above intervened BMDC with CD4+ T cells, and treat B16 melanoma cells with the co-culture supernatant. Our study will reveal the molecular mechanism of curcumin inhibiting Th17 differentiation and promoting melanogenesis through the mGluR4/cAMP/PTEN axis. Finally, based on the establishment of a mouse model of vitiligo, the mechanism of curcumin promoting melanogenesis will be clarified. This study will be systematically carried out at the animal, cell, and molecular levels, contributing to the revelation of the neuro-immune pathogenesis of vitiligo, providing new strategies for the integrated treatment of vitiligo with traditional Chinese and Western medicine.